Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-managed, section 3 trial



Summary

Background

Cardiac muscle hypercontractility is a key pathophysiological abnormality in hypertrophic
cardiomyopathy, and a serious determinant of dynamic left ventricular outflow tract
(LVOT) obstruction. In the market pharmacological choices for hypertrophic cardiomyopathy
are insufficient or poorly tolerated and are no longer disease-explicit. We aimed to assess
the efficacy and security of mavacamten, a first-in-class cardiac myosin inhibitor,
in symptomatic obstructive hypertrophic cardiomyopathy.

Methods

On this section 3, randomised, double-blind, placebo-managed trial (EXPLORER-HCM)
in 68 medical cardiovascular centres in 13 worldwide locations, patients with hypertrophic
cardiomyopathy with an LVOT gradient of 50 mm Hg or increased and Recent York Coronary heart Affiliation
(NYHA) class II–III symptoms were assigned (1:1) to acquire mavacamten (beginning at
5 mg) or placebo for 30 weeks. Visits for evaluate of affected person site befell each and each
2–4 weeks. Serial reports incorporated echocardiogram, electrocardiogram, and blood
collection for laboratory exams and mavacamten plasma concentration. The principle endpoint
changed into a 1·5 mL/kg per min or increased extend in peak oxygen consumption (pVO
2) and no longer no longer as much as one NYHA class discount or a 3·0 mL/kg per min or increased pVO
2extend with out NYHA class worsening. Secondary endpoints assessed adjustments in post-articulate
LVOT gradient, pVO
2, NYHA class, Kansas Metropolis Cardiomyopathy Questionnaire-Scientific Summary Win (KCCQ-CSS),
and Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness-of-Breath subscore
(HCMSQ-SoB). This watch is registered with
ClinicalTrials.gov,
NCT03470545.

Findings

Between Would perchance well 30, 2018, and July 12, 2019, 429 adults were assessed for eligibility,
of whom 251 (59%) were enrolled and randomly assigned to mavacamten (n=123 [49%])
or placebo (n=128 [51%]). 45 (37%) of 123 patients on mavacamten versus 22 (17%) of
128 on placebo met the predominant endpoint (difference +19·4%, 95% CI 8·7 to 30·1; p=0·0005).
Sufferers on mavacamten had increased reductions than these on placebo in post-articulate
LVOT gradient (−36 mm Hg, 95% CI −43·2 to −28·1; p2(+1·4 mL/kg per min, 0·6 to 2·1; p=0·0006), and improved symptom ratings (KCCQ-CSS
+9·1, 5·5 to 12·7; HCMSQ-SoB −1·8, −2·4 to −1·2; pvs40 of 128 patients in the placebo neighborhood; 95% CI 22·2 to 45·4; p

Interpretation

Remedy with mavacamten improved articulate capacity, LVOT obstruction, NYHA life like
class, and properly being site in patients with obstructive hypertrophic cardiomyopathy.
The outcomes of this pivotal trial highlight the advantages of disease-explicit treatment
for this situation.

Funding

MyoKardia.

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Article Files

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Printed: August 29, 2020

Identification

DOI:https://doi.org/10.1016/S0140-6736(20)31792-X

Copyright

© 2020 Elsevier Ltd. All rights reserved.

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